MTHFR (methylenetetrahydrofolate reductase: EC 1.5.1.20) SNPs (single-nucleotide polymorphisms) and homocysteine in patients referred for investigation of fertility

Ménézo, Yves; Patrizio, Pasquale; Álvarez, Silvia; Amar, Edouard; Brack, Michel; Brami, C.; Chouteau, J.; Clément, Arthur; Clément, Patrice; Cohen, Marc; Cornet, D.; Dale, Brian; Amato, Guiseppe D'; Jacquesson-Fournols, Laetitia; Marès, P.; Neveux, Paul; Sage, Jean Clement; Servy, Edouard; Huong, To Minh; Viot, Géraldine

doi:10.1007/s10815-021-02200-6

Cited by 12 publications

(8 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Combined with the results that homozygous mutation of MTHFR 677TT, significantly reduced the number of good-quality embryos, we speculated that MTHFR 677TT mutation may affect pregnancy outcomes mainly by decreasing embryo quality. Besides, increasing evidence indicates that the T allele of the C677T MTHFR polymorphism is associated with hyperhomocysteinemia [ 32 – 35 ], vitamin D concentrations and natural killer cell cytotoxicity [ 16 ], all of these factors could affect reproductive outcomes.…”

Section: Discussionmentioning

confidence: 99%

MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study

Zeng

Liu

Zhang

et al. 2022

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

Background Whether MTHFR C677T genotype affects pregnancy outcomes following assisted reproductive technology is conflicting. And the role of MTHFR C677T genotype on cumulative live birth has not been reported. This study aims to investigate the effect of MTHFR C677T genotype on cumulative live birth following in-vitro fertilization and embryo transfer (IVF-ET). Methods This is a retrospective cohort study that includes 1173 women undergoing their first IVF-ET. We retrospectively compared the reproductive outcomes among the groups stratified by MTHFR C677T genotypes (677CC, 677CT, 677TT). We performed interaction analysis to detect the factor that interacts with the MTHFR C677T genotype. Poisson regression analyses were used to evaluate the associations between MTHFR C677T genotypes with the number of transferable embryos and the number of good-quality embryos. Cox regression analysis was used to evaluate the association between MTHFR C677T genotypes with cumulative live birth. All regression analyses were adjusted with the confounding factors which may independently impact reproductive outcomes. Results There is a significant interactive effect of MTHFR 677TT genotype with GnRHa protocol on reproductive outcomes (P for interaction<0.05). MTHFR 677TT homozygous mutation was found to impact reproductive outcomes under GnRHa short protocol but not GnRHa long protocol. MTHFR 677TT is significantly associated with decreased number of transferable embryos (p-value=0.028), decreased number of good-quality embryos (p-value=0.005), and decreased cumulative live birth rate (p-value=0.024) in patients undergoing GnRHa short protocol. However, the clinical pregnancy rate, miscarriage rate and live birth rate at the first embryo transfer cycle were not significantly different between the groups under both protocols (p-values>0.05). Conclusions MTHFR 677TT genotype is associated with decreased number of transferable embryos, decreased number of good-quality embryos, and decreased cumulative live birth rate in the first complete cycle in patients undergoing GnRHa short protocol.

show abstract

Section: Discussionmentioning

confidence: 99%

MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study

Zeng

Liu

Zhang

et al. 2022

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

show abstract

“…A decrease in the activity in terms of 5-MTHF formation can reach −60% for C677T (a thermolabile variant) and −40% for C1298C homozygotes [ 7 , 8 ], causing a reduction in blood folate concentration [ 9 ]. Combined heterozygotes C677T/A198C are at risk, and a rather high proportion of the carriers of this combination have an elevated Hcy [ 10 ]. These SNPs are highly prevalent as heterozygotes, but homozygous T677T can easily reach 25% in certain populations (Iran, China, Turkey, Spain, Southern Italy).…”

Section: The One Carbon (1-cc) and The Folates Cycle (Fc)mentioning

confidence: 99%

“…This shortage is exacerbated in the presence of MTHFR SNPs, with an impact on male and female fertility. There is significant sex variation to this feature, and pathologies are not fully linked to increased levels of homocysteine [ 10 ]. In recent years, risks associated with FA supplementation and UMFA have also been highlighted.…”

Section: Folate Malabsorptionmentioning

confidence: 99%

See 1 more Smart Citation

Folic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles

Ménézo¹,

Elder

Clément³

et al. 2022

Biomolecules

Self Cite

View full text Add to dashboard Cite

Methylation is an essential biochemical mechanism that is central to the transmission of life, and crucially responsible for regulating gametogenesis and continued embryo development. The methylation of DNA and histones drives cell division and regulation of gene expression through epigenesis and imprinting. Brain development and its maturation also depend on correct lipid methylation, and continued neuronal function depends on biogenic amines that require methylation for their synthesis. All methylation processes are carried out via a methyltransferase enzyme and its unique co-factor S-adenosylmethionine (SAM); the transfer of a methyl group to a target molecule results in the release of SAH (SA homocysteine), and then homocysteine (Hcy). Both of these molecules are toxic, inhibiting methylation in a variety of ways, and Hcy recycling to methionine is imperative; this is achieved via the one carbon cycle, supported by the folates cycle. Folate deficiency causes hyperhomocysteinaemia, with several associated diseases; during early pregnancy, deficiency interferes with closure of the neural tube at the fourth week of gestation, and nutraceutical supplementation has been routinely prescribed to prevent neural tube defects, mainly involving B vitamins, Zn and folates. The two metabolic pathways are subject to single nucleotide polymorphisms that alter their activity/capacity, often severely, impairing specific physiological functions including fertility, brain and cardiac function. The impact of three types of nutraceutical supplements, folic acid (FA), folinic acid (FLA) and 5 Methyl THF (MTHF), will be discussed here, with their positive effects alongside potentially hazardous secondary effects. The issue surrounding FA and its association with UMFA (unmetabolized folic acid) syndrome is now a matter of concern, as UMFA is currently found in the umbilical cord of the fetus, and even in infants’ blood. We will discuss its putative role in influencing the acquisition of epigenetic marks in the germline, acquired during embryogenesis, as well as the role of FA in the management of cancerous disease.

show abstract

“…Variant c.677T (rs1801133) causes a 70% reduction in enzyme activity [ 83 ]. Each copy of the low-activity T allele causes a greater reduction in folate and a higher level of homocysteine [ 84 , 85 ]. Initial reports found an elevated risk of IBD in carriers of the TT genotype, but the majority of subsequent studies, including high-quality studies, did not corroborate this finding [ 55 , 78 ]; however, further research is needed.…”

Section: Role Of Vitamins In Inflammatory Bowel Diseasementioning

confidence: 99%

Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease

Dragašević

Stanković

Kotur

et al. 2022

Life

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are complex diseases whose etiology is associated with genetic and environmental risk factors, among which are diet and gut microbiota. To date, IBD is an incurable disease and the main goal of its treatment is to reduce symptoms, prevent complications, and improve nutritional status and the quality of life. Patients with IBD usually suffer from nutritional deficiency with imbalances of specific micronutrient levels that contribute to the further deterioration of the disease. Therefore, along with medications usually used for IBD treatment, therapeutic strategies also include the supplementation of micronutrients such as vitamin D, folic acid, iron, and zinc. Micronutrient supplementation tailored according to individual needs could help patients to maintain overall health, avoid the triggering of symptoms, and support remission. The identification of individuals’ genotypes associated with the absorption, transport and metabolism of micronutrients can modify future clinical practice in IBD and enable individualized treatment. This review discusses the personalized approach with respect to genetics related to micronutrients commonly used in inflammatory bowel disease treatment.

show abstract

MTHFR (methylenetetrahydrofolate reductase: EC 1.5.1.20) SNPs (single-nucleotide polymorphisms) and homocysteine in patients referred for investigation of fertility

Cited by 12 publications

References 45 publications

MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study

MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study

Folic Acid, Folinic Acid, 5 Methyl TetraHydroFolate Supplementation for Mutations That Affect Epigenesis through the Folate and One-Carbon Cycles

Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease

Contact Info

Product

Resources

About